A hydrophobic barrier deep within the inner pore of the TWIK-1 K2P potassium channel
Prafulla Aryal,
Firdaus Abd-Wahab,
Giovanna Bucci,
Mark S. P. Sansom () and
Stephen J. Tucker ()
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Prafulla Aryal: Clarendon Laboratory, University of Oxford
Firdaus Abd-Wahab: Clarendon Laboratory, University of Oxford
Giovanna Bucci: Clarendon Laboratory, University of Oxford
Mark S. P. Sansom: University of Oxford
Stephen J. Tucker: Clarendon Laboratory, University of Oxford
Nature Communications, 2014, vol. 5, issue 1, 1-9
Abstract:
Abstract Recent X-ray crystal structures of the two-pore domain (K2P) family of potassium channels have revealed a unique structural architecture at the point where the cytoplasmic bundle-crossing gate is found in most other tetrameric K+ channels. However, despite the apparently open nature of the inner pore in the TWIK-1 (K2P1/KCNK1) crystal structure, the reasons underlying its low levels of functional activity remain unclear. In this study, we use a combination of molecular dynamics simulations and functional validation to demonstrate that TWIK-1 possesses a hydrophobic barrier deep within the inner pore, and that stochastic dewetting of this hydrophobic constriction acts as a major barrier to ion conduction. These results not only provide an important insight into the mechanisms which control TWIK-1 channel activity, but also have important implications for our understanding of how ion permeation may be controlled in similar ion channels and pores.
Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5377
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DOI: 10.1038/ncomms5377
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